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1113 citation(s) found for "Wu, Robin".

The ARTFL LEFFTDS Frontotemporal Lobar Degeneration (ALLFTD) Protocol: Preliminary Data and Future Plans (2081)
Boxer, Adam L. , Rosen, Howard, Forsberg, Leah K. , Heuer, Hilary W. , Brushaber, Danielle , Bordelon, Yvette , Dickerson, Bradford, Dickinson, Susan, Faber, Kelley , Fagan, Anne M. , Fields, Julie A. , Fishman, Ann, Gavrilova, Ralitza H. , Gendron, Tania, Geschwind, Daniel H. , Ghoshal, Nupur , Graff‐Radford, Jonathan , Graff‐Radford, Neill R. , Grant, Ian , Huey, Edward D. , Karydas, Anna, Kaufer, Daniel , Kramer, Joel H. , Kornak, John , Lagone, Emma, Ljubenkov, Peter A. , Lucente, Diane , Mackenzie, Ian R. , Manoochehri, Masood , Masdeu, Joseph C. , McGinnis, Scott, Mendez, Mario F. , Miller, Bruce, Miyagawa, Toji , Nelson, K. , Onyike, Chiadi U. , Pearlman, Rodney , Petrucelli, Leonard , Rademakers, Rosa , Ramos, Eliana Marisa , Rankin, Katherine P. , Rascovsky, Katya, Ritter, Aaron, -Martinez, Julio Rojas, Sabbagh, Marwan N. , Salmon, David P. , Savica, Rodolfo , Staffaroni, Adam M. , Syrjanen, Jeremy A. , Tatton, Nadine , Taylor, Joanne, Toga, Arthur W. , Weıntraub, Sandra , Wheaton, Diana, Boeve, Bradley F. , Appleby, Brian S. , Biernacka, Joanna M. , Botha, Hugo , Brannelly, Patrick , Dickson, Dennis W. , Domoto‐Reilly, Kimiko , Foroud, Tatiana , Galasko, Douglas , Gendron, Tania F. , Goldman, Jill , Grossman, Murray , Hsiung, Ging‐Yuek Robin , Huang, Eric J. , Irwin, David J. , Jones, David T. , Kantarci, Kejal , Knopman, David S. , Kremers, Walter K. , Kukull, Walter A. , Litvan, Irene , Masdeu, Joseph C , Nelson, Kevin, Pantelyat, Alexander , Pascual, Belén , Rexach, Jessica E. , Roberson, Erik D. , Seeley, William W. , Tartaglia, Maria Carmela , Wong, Bonnie , Wszołek, Zbigniew K.

Neurology | December 7, 2023 | Volume: 94 | Issue: 15_supplement | Pages: No page available

10.1212/wnl.94.15_supplement.2081 Get It

Altered resting-state network connectivity in stroke patients with and without apraxia of speech (S49.002)
New, Anneliese , Kirrie, Ballard, Parkinson, Amy, McNeil, Malcolm, Price, Cathy J. , Robin, Donald A., Duffy, Joseph R. , Piguet, Olivier , Hornberger, Michael , Eickhoff, Simon Bodo

Neurology | December 6, 2023 | Volume: 84 | Issue: 14_supplement | Pages: No page available

10.1212/wnl.84.14_supplement.s49.002 Get It

The Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Protocol: Known Kindreds and Preliminary Data (P5.003)
Rosen, Howard, Boxer, Adam L. , Ghoshal, Nupur , Graff‐Radford, Neill R. , Huey, Edward D. , Kornak, John , Mackenzie, Ian R. , Petrucelli, Leonard , Rademakers, Rosa , Shaw, Leslie M. , Toga, Arthur W. , Trojanowski, John Q. , Boeve, Bradley F. , Dickerson, Bradford Clark , Feldman, Howard , Goldman, Jill , Grossman, Murray , Hsiung, Ging‐Yuek Robin , Irwin, David J. , Jack, Clifford R. , Kantarci, Kejal , Knopman, David S. , Miller, Bruce L. , Wszołek, Zbigniew K.

Neurology | December 6, 2023 | Volume: 84 | Issue: 14_supplement | Pages: No page available

10.1212/wnl.84.14_supplement.p5.003 Get It

Safety and Preliminary Efficacy of Sabestomig (AZD7789), an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma Previously Treated with Anti-PD-(L)1 Therapy
Corazzelli, Gaetano , Morschhauser, F., Lee, Hun Ju , Ansell, S., Moskowitz, Craig H. , Johnson, Nathalie A. , Hutchings, Martin , Casterá, María José Terol, Hawkins, George, Vossenkaemper, Anna, Collins, Teresa , Lesley, Robin, Yu, Ting , Hall, Connor P. , Cérec, Virginie, Mei, Matthew , Phillips, Elizabeth H. , Collins, Graham P. , Kuruvilla, John , Hawkins, George, Dean, Emma , Yu, Ting, Zinzani, Pier Luigi

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 4433-4433

10.1182/blood-2023-180926 Get It

Background Immunotherapies targeting the PD-1/PD-L1 pathway have been shown to induce high response rates in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). However, most responses are partial and not durable. T cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is implicated as a resistance mechanism following anti-PD-1 therapy, and increased TIM-3 expression has been observed on T cells of patients with cHL post anti-PD-1 therapy. Therefore, we hypothesized that dual targeting of PD-1 and TIM-3 may reinvigorate immune responses and lead to more durable antitumor activity. Sabestomig is a monovalent, bispecific, humanized IgG1 monoclonal antibody that binds PD-1 and a unique epitope in the TIM-3 IgV domain without blocking phosphatidylserine binding, eliciting differential functionality. In preclinical mouse models, sabestomig was more effective at inhibiting growth of solid tumors than treatment targeting only PD-1, and sequential sabestomig after anti-PD-1 therapy increased antitumor responses. Here we report preliminary data from the ongoing dose escalation portion of a Phase I/II, open-label, multicenter study to assess the safety and preliminary efficacy of sabestomig in patients with r/r cHL (NCT05216835). Methods Eligible patients are aged ≥16 years with r/r cHL, an Eastern Cooperative Oncology Group performance status 0-1, at least one positron emission tomography-avid measurable lesion according to modified Lugano Criteria, and exposure to at least 2 prior lines of systemic therapy including a minimum of 3 cycles of an anti-PD-(L)1-based therapy. Sabestomig is intravenously infused over 1 hour following pretreatment with diphenhydramine and acetaminophen every 3 weeks, with planned doses ranging from 2 to 2000 mg across 8 cohorts (A1-A8); cohorts A1 to A4 (2, 7, 22.5 or 75 mg) follow an accelerated titration design with a single patient treated at each dose level, while cohorts A5 to A8 (225-2000 mg) follow a modified toxicity probability interval-2 algorithm. The primary endpoint of the dose escalation part of the study is safety, including dose-limiting toxicities (DLTs). Secondary endpoints include efficacy, pharmacokinetics, and immunogenicity. Data cutoffs were May 17, 2023 for safety and June 20, 2023 for efficacy. Results As of May 17, 2023, 14 patients were treated across the first 6 cohorts (A1-A6; 2-750 mg). They were predominantly male (64.3%) with Stage IV disease (85.7%) and a median age of 41.5 years (range, 25-77). Patients received a median of 6 prior lines of therapy (range, 3-13). Baseline disease characteristics are summarized in Table 1. Four patients received sabestomig 2-75 mg in cohorts A1-A4 (n=1 each), 5 patients received 225 mg in cohort A5, and 5 patients received 750 mg in cohort A6. Median duration of exposure to sabestomig was 8.9 weeks (range, 3.0-34.3) with a median of 3 cycles received (range 1-12). Sabestomig was well tolerated with no Grade ≥3 treatment-related adverse events (AEs) (Table 2). One Grade ≥3 AE occurred, which was fatal (sepsis secondary to gastric ulcer rupture, not related to sabestomig but deemed a DLT by the safety review committee). No immune-mediated AEs were reported, and no AEs led to treatment discontinuation. At the safety data cutoff, treatment was ongoing for 6 patients (42.9%). As of June 20, 2023, 11 patients had their first disease assessment and 4/11 had an objective response based on modified Lugano Criteria: 1 patient in cohort A3 (22.5 mg, a partial response [PR]) and all 3 patients who had their first disease assessment in cohort A6 (750 mg, 2 CRs and 1 PR). Two of these 4 responders (both in cohort A6) had experienced a best overall response of progressive disease during prior anti-PD-1 therapy; the other two initially had a response (1 CR [cohort A6] and 1 PR [cohort A3]) but subsequently progressed on anti-PD-1 therapy. Sustained PD-1 receptor occupancy (≥90%) was observed in peripheral blood at doses ≥225 mg. Conclusions Sabestomig was well tolerated with a manageable safety profile. Early efficacy data at 750 mg is encouraging with objective responses in 3/3 patients who had their first disease assessment, including those who were anti-PD-1 refractory or who relapsed on treatment. Updated data will be presented from ongoing and subsequent patients treated during dose escalation with doses of up to 2000 mg.
Transplacental Transfer of Emicizumab: Experience with Emicizumab in a Pregnant Female with Severe Hemophilia Α and an Inhibitor
Kharel, Zeni , Pruthi, Rajiv K. , Reid, Robin, Kouides, Peter A. , Reid, Robin

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 5492-5492

10.1182/blood-2023-190012 Get It

Introduction: Severe hemophilia A (HA) in females is incredibly rare particularly if complicated by a high-titer factor VIII (FVIII) inhibitor. We report, to the best of our knowledge, the first-of-its-kind use of emicizumab (emi) ante/post-partum, its effect on the newborn, and its excretion in breast milk. Baseline details: 29-year-old-female was diagnosed with severe HA at age 1 following prolonged bleeding from a venipuncture site. She had no family history of HA. One stage FVIII activity (OSA) was less than 1%. She was compound heterozygous for F8 type 1 and type 2 intron 22 inversions. At 21 months of age, she developed a high-titer inhibitor (peak: 35 Bethesda unit[BU]). She was not treated with immune tolerance induction and had remained on factor eight inhibitor bypassing activity (FEIBA) as prophylaxis until transferring to our center. She was transitioned to monthly emi prophylaxis and recombinant FVIIa (rFVIIa, NovoSeven) for breakthrough bleeding at age 26. She was medically advised against pregnancy due to unclear safety profile of emi in pregnancy and theoretical concerns for an increased risk of bleeding and thrombotic complications associated with the use of bypassing agents in the peripartum setting. Nevertheless, she desired pregnancy and continued on emi prophylaxis every 4 weeks during her pregnancy. Clinical course in pregnancy: She had an uncomplicated antepartum course and did not require rFVIIa for breakthrough bleeds. Blood emi levels and FVIII inhibitor levels were measured in each trimester of pregnancy (Table 1). Her labor was induced with oxytocin while on rFVIIa and tranexamic acid (TXA) support. She had a spontaneous, unassisted vaginal delivery immediately complicated by post-partum hemorrhage resulting in estimated blood loss of 1100cc. She did not require blood transfusion. She continued on 90 mcg/kg rFVIIa support every 2 hours, gradually prolonging the dosing interval by 2 hours every 24 hours (q2, q4, q6, etc.), and experienced no further in-hospital bleeding. She delivered a healthy female newborn. The infant developed cephalhematoma but transcranial ultrasound was negative for intracranial bleeding. Cord blood was collected at the time of delivery and sent for emi level, FVIII activity and FVIII inhibitor titer (Table 2). FVIII inhibitor assay with bovine reagent (CBU) was performed using chromogenic substrate assay (CSA) after pre-analytical heat-inactivation of patient plasma. The infant's CSA FVIII level was measured using a bovine chromogenic FVIII assay, and FVIII was also assayed using a one-stage APTT-based assay. Mother opted to breast-feed the infant. Emi level was measured in breast milk (Table 1). Conclusion: In this highly unusual case, we demonstrate that emi crossed the placenta and is excreted in breast milk. We also demonstrate that the maternal FVIII inhibitor did not cross the placenta into the newborn. Drawing conclusions on the safety of emi despite placental and breast milk transmission and transmissibility of inhibitor based on a single case would be premature. The conglomeration of several rarities in a single case renders our report unique and insightful and provides a baseline experience for future cases.
A First in Human Phase I Trial (LS1681) of Abraxane/Rituximab 160 Nm Nanoparticle (AR160) in Relapsed Refractory B-Cell Lymphomas Including Transformed Follicular Lymphoma: A Final Report
LaPlant, Betsy, Micallef, Ivana N. , Finnes, Heidi D. , Klebig, Robin, Hanley, Nikki, King, Rebecca L. , Habermann, Thomas M. , Schimke, Jill M. , Witzig, Thomas E. , Markovic, Svetomir N.

Blood | December 1, 2023 | Volume: 142 | Issue: Supplement 1 | Pages: 4471-4471

10.1182/blood-2023-175014 Get It

Introduction: Nanotechnology for cancer therapy aims to increase drug delivery to tumor sites while lowering toxicity. AR160 is a novel 160 nm nano-immunoconjugate consisting of commercial grade nab-paclitaxel (NP) nanoparticles non-covalently coated with rituximab (R) for targeted delivery into tissues expressing CD20. The drug delivery system and clinical grade product was developed in the laboratory of Svetomir N. Markovic, M.D.,Ph.D. Single agent rituximab at a dose of 375 mg/m 2 in relapsed patients with aggressive lymphomas is not utilized and has limited activity in patients with multiple relapses. Taxanes (Younes 1995, Wilson 1995) have modest clinical activity as a single agent with overall response rates of 23% and 17%, respectively, when administered at doses of 200 mg/m 2 and 140 mg/m 2 in previously treated patients with non-Hodgkin lymphoma (NHL). We hypothesized that utilizing the targeted ability of rituximab that the AR160 taxane nanoparticle would have activity in relapsed B-cell NHL and offer a new class of agents for relapsed B-cell NHL. Methods: A 3+3 phase I clinical trial was conducted in patients with relapsed refractory non-Hodgkin lymphoma to determine the maximum tolerated dose of AR160 administered intravenously on days 1, 8, and 15 of a 28-day cycle. Patients were required to have had prior systemic treatment with no other therapy with clinical benefit. Patients with aggressive lymphoma were required to have a stem cell transplant if transplant eligible. AR160 was prepared on-site in the Mayo Clinic Cancer Center Research Pharmacy, and the product was reconstituted by mixing the two agents delivering as one combined infusion at a specific concentration. The starting dose level (DL1) was NP at 100mg/m 2 with R at 40 mg/m 2. These doses were significantly lower than standard doses. Disease evaluations were conducted after every 2 treatment cycles using CT based criteria from the revised 2014 Lugano Classification or PET scans. Patients were treated until disease progression or intolerability. Samples were collected for pharmacokinetic (PK) studies. Results: Nine (7 males and 2 females) patients with a median age of 61 (range 55-84 years) were enrolled (2 follicular lymphoma (FL), 1 previously transformed from FL to diffuse large B-cell lymphoma (DLBCL) followed by FL relapse, 1 high-grade B-cell lymphoma with MYC and BCL2 rearrangements transformed from FL, 1 transformed FL to DLBCL, 2 high-grade B-cell lymphoma with MYC and BCL2 rearrangements, 1 high-grade B-cell lymphoma NOS and 1 mantle cell lymphoma. The median number of prior treatments was 4 (range 3-16). At dose level 1, all 3 of the first 3 patients experienced grade 3 or 4 neutropenia (C1D15, C4D1, and C1D15) with the C4D1 a grade 4 and unlikely related. After the first three patients, de-escalation to dose level -1 was implemented per protocol with NP at 75 mg/m 2 and rituximab at 30 mg/m 2. There was one patient with a grade 3 non-hematological adverse event all possibly related to treatment (anorexia, diarrhea, and enterocolitis). There were 6 partial responses (71%), 1 complete response (14%) with high-grade B-cell lymphoma with MYC and BCL2 rearrangement, 1 stable disease with mantle cell lymphoma and 1 patient had progressive disease. Six of the 9 patients were alive with subsequent therapies. PK evaluation is pending. Conclusion: AR160 therapy is a novel drug delivery system incorporating significantly lower doses of paclitaxel and rituximab that is safe and demonstrates promising clinical activity in patients with low-grade and high-grade previously treated B-cell lymphomas. This principle of treatment is applicable to other disorders. Further clinical testing is warranted in these patient populations.
857. Impact of Rapid Antibiotic Susceptibility Testing for Gram Negative Bacteremia Varies by Pathogen Type and Resistance: A Secondary Analysis of the RAPIDS GN Trial
Banerjee, Ritu , Giri, Abhigya, Komarow, Lauren , Souli, Maria , Doernberg, Sarah B. , Patel, Robin

Open Forum Infectious Diseases | November 27, 2023 | Volume: 10 | Issue: Supplement_2 | Pages: No page available

10.1093/ofid/ofad500.902 Get It

Abstract Background The RAPIDS GN trial, a prospective randomized controlled trial, showed that rapid blood culture antibiotic susceptibility testing (AST) led to faster antibiotic therapy changes compared to standard of care (SOC) testing for Gram negative bacteremia (Banerjee et al, Clin Infect Dis (2021) 73:e39-e46). A secondary analysis of the data was conducted to assess impact of rapid testing on appropriateness of antibiotic spectrum by pathogen and resistance profile. Empiric treatment (0 to 2 h post randomization) among subjects with antibiotic-susceptible isolates of monomicrobial, on-panel Gram negative species (N = 320). For this analysis subjects from both SOC and rapid testing groups were included. Black: Excluded from treatment definition if subjects received no antibiotics, antibiotics without susceptibility results reported, or only an aminoglycoside, azithromycin, penicillin, rifaximin, or atovaquone. Antibiotic treatment appropriateness for antibiotic-susceptible Escherichia coli, and Klebsiella and Proteus isolates (N= 240) by time after randomization and treatment arm. Black: Excluded from treatment definition if subjects received no antibiotics, antibiotics without susceptibility results reported, or only an aminoglycoside, azithromycin, penicillin, rifaximin, or atovaquone. AXDX, rapid susceptibility testing group. Methods Subjects enrolled in the RAPIDS GN trial who had blood cultures with monomicrobial Gram negative bacilli that were “on-panel” for the rapid test were included. Antibiotics administered from randomization (0 h) through 52 h were evaluated. Antibiotic therapy was classified based on SOC AST as: undertreatment (antibiotic to which the blood isolate was resistant), appropriate treatment (narrowest spectrum antibiotic to which the blood isolate was susceptible), and overtreatment [overly broad-spectrum antibiotic(s) based on blood isolate AST]. Antibiotic-resistant isolates were defined as 3rd generation cephalosporin non-susceptible or carbapenem-resistant isolates. Antibiotic treatment appropriateness for antibiotic-resistant (3rd generation cephalosporin non-susceptible or carbapenem-resistant) Escherichia coli, and Klebsiella and Proteus isolates (N= 50) by time after randomization and treatment arm. Black: Excluded from treatment definition if subjects received no antibiotics, antibiotics without susceptibility results reported, or only an aminoglycoside, azithromycin, penicillin, rifaximin, or atovaquone. AXDX, rapid susceptibility testing group. Results 388/448 (87%) subjects were included (197 SOC, 191 rapid). Among susceptible isolates, between 0 through 2 h post-randomization (before AST results), overtreatment was more common for Escherichia coli, and Klebsiella and Proteus species than for other species (72% vs. 41%, p ≤0.001; Fig 1). Among 290 E. coli, Klebsiella and Proteus isolates, treatment appropriateness improved with time after randomization in both SOC and rapid testing groups. The proportion with appropriate treatment was higher in the rapid testing group than the SOC group at all time points after 24 h post-randomization and differed by resistance. Overtreatment was common for susceptible isolates while undertreatment was common for resistant isolates (Fig. 2 and 3). Among resistant isolates, by 52 h post-randomization undertreatment decreased to 15% in the rapid testing group but only 35% in the SOC group (Fig 3). Conclusion In the RAPIDS GN trial, rapid AST had the greatest benefit on management of antibiotic-resistant E. coli, Klebsiella, and Proteus bacteremia. These findings can inform antibiotic stewardship and design of future blood culture diagnostic trials. Disclosures Ritu Banerjee, MD, Ph.D, bioMerieux: Grant/Research Support|bioMerieux: company is providing partial support for an ongoing trial unrelated to submitted abstract Sarah B. Doernberg, MD, MAS, Basilea: Clinical events committee/adjudication committee participation|F2G: Grant/Research Support|Genentech: Advisor/Consultant|Gilead: Grant/Research Support|Janssen/J+J: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Shinogi: Clinical events committee/adjudication committee participation Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant
215. Shorter vs. Longer Duration of Treatment in Patients with Ceftriaxone-resistant and Ceftriaxone-susceptible Escherichia coli Bloodstream Infections
Mackow, Natalie , Ge, Lizhao , Komarow, Lauren , Shao, Wanying, Herc, Erica , Arias, César A. , Satlin, Michael J. , Dhar, Sorabh , Shelburne, Samuel A. , Hill, Carol , Greenwood‐Quaintance, Kerryl E. , Schmidt-Malan, Suzannah M., Fowler, Vance G. , Doi, Yohei , Arias, César A. , Albin, Owen , Saade, Elie , Miller, Loren G , Jacob, Jesse T. , Kršák, Martin , Huskins, W. Charles , Patel, Robin , Fowler, Vance G. , Tamma, Pranita D. , van Duin, David

Open Forum Infectious Diseases | November 27, 2023 | Volume: 10 | Issue: Supplement_2 | Pages: No page available

10.1093/ofid/ofad500.288 Get It

Abstract Background Several randomized controlled trials (RCT) have shown that short-course (∼7 days) antibiotic treatment is non-inferior to longer antibiotic courses (∼14 days) in patients with uncomplicated bloodstream infection (BSI) with mostly susceptible Gram-negative bacteria. Here, we evaluate short-course therapy in ceftriaxone-resistant E. coli BSI. Methods In a prospective cohort of 300 patients with E. coli BSI at 14 United States hospitals between November 2020 and April 2021, each patient with ceftriaxone-R E. coli BSI, and the next consecutive patient with a ceftriaxone-S E. coli BSI was included. Patients who received 5-8 days (“short”) or 9-21 days (“long”) of antibiotics were included in this analysis. Patients who died before day 9 were excluded. Primary outcome was a Desirability of Outcome Ranking (DOOR, Table 1) based on disposition at day 30 after collection of the index blood culture. Ceftriaxone susceptibility was centrally determined using broth microdilution for all bacterial isolates. Desirability of outcome ranking (DOOR) categories Results Of 300 patients in the original cohort, 227 were included; 44 patients (24 ceftriaxone-S, 20 ceftriaxone-R) received short (median 8 days, range 5-8 days), and 183 patients (96 ceftriaxone-S, 87 ceftriaxone-R) received long duration (median 15 days, range 9-21 days). Age (median 68 years, IQR 57-77 years), sex (125/227 [55%] female), and Charlson comorbidity index (median 2, IQR 1-4) were similar between groups. Notably, almost all patients (18/19, 95%) with solid organ or stem cell transplant were in the long duration group. The median Pitt bacteremia score was 2 (IQR 1-3) in the short duration group vs. 1 (IQR 0-3) in the long duration group (Wilcoxon Rank Sum p=0.07). DOOR outcomes were similar in both groups (Figure and Table 2). Numerically more patients in the ceftriaxone-resistant group on short treatment were in category 3; 4/20 (20%) vs 5/87 (6%) in the long duration group. These 4 patients all had unsuccessful discharge combined with renal failure (n=2), and/or lack of clinical response (n=3). Desirability of outcome ranking (DOOR) analysesFigure.DOOR outcomes Shown are the percentages of patients in each group with a specific DOOR category outcome. Conclusion Short duration of therapy was less frequently used than long duration of therapy in this prospective cohort of E. coli BSI. Further studies are needed to determine whether short-course therapy is appropriate for ceftriaxone-R E. coli BSI. Disclosures Yohei Doi, MD, PHD, bioMerieux: Advisor/Consultant|FujiFilm: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria Owen Albin, MD, Charles River Laboratories: Advisor/Consultant|Shionogi: Advisor/Consultant Elie Saade, MD, MPH, FIDSA, Envision Pharma: Speaker, Presenter|Johnson and Johnson: Speaker, Travel, Lodging|Protein Sciences Corp: Grant/Research Support|Sanofi Pasteur: Speaker, Travel and Lodging Loren G. Miller, MD MPH, ContraFect: Grant/Research Support|GSK: Grant/Research Support|Medline: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support Michael J. Satlin, MD, AbbVie: IDMC member|Biomerieux: Grant/Research Support|Merck: Grant/Research Support|Shionogi: Advisor/Consultant|SNIPRBiome: Grant/Research Support Martin Krsak, MD, MSc, FASAM, AbbVie: Grant/Research Support|Melinta: Honoraria W. Charles Huskins, MD, MSc, ADMA Biologics: Advisor/Consultant|Bristol Myers Squibb: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds|Zimmer Biomet: Stocks/Bonds Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant Vance G. Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant
2143. in-vitro activity of Bacteriophages against Methicillin-Resistant Staphylococcus aureus Biofilms
Chaudhry, Waqas , Fackler, Joseph , Sowers, John M, Vadlamudi, Aravinda, Greenwood‐Quaintance, Kerryl E. , Parmar, Krupa , Patel, Robin

Open Forum Infectious Diseases | November 27, 2023 | Volume: 10 | Issue: Supplement_2 | Pages: No page available

10.1093/ofid/ofad500.1766 Get It

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) biofilms can be resilient to the human immune system and antibiotics, a challenge augmented by acquired antimicrobial resistance. Phage therapy is being evaluated for biofilm-associated infections. Methods Here, model phages SaMD07ø1 and SaRB105030ø5 were evaluated against their hosts SaMD07 and SaRB105030, respectively, grown as biofilms in 96-well plates, as biofilms on glass beads and planktonically. Trypticase soy broth (TSB) and phosphate buffered saline (PBS) were evaluated as testing media (Figure 1). Biofilms were incubated with phages in the presence of media containing tetrazolium dye in 96-well plates and assessed for hold times (delays in reaching bacterial log-phase metabolic activity compared to controls) over 48 hours (h) using a Biolog Omnilog® system and by assessing colony forming units (CFUs). Subsequently, using the beads biofilm assay in TSB medium performed on the Omnilog® (BBTO) (Figure 2), test phage SaMD22ø1 was evaluated in quintuplicate against biofilms formed by MRSA isolates IDRL-6130, IDRL-6927, IDRL-6987, IDRL-7381, IDRL-7542 and IDRL-10947, all recovered from periprosthetic joint infection. Test phage K was evaluated against GFP-labelled MRSA AH1263 using BBTO method and simultaneously by fluorescence microscopy.Figure 1.Biofilm phage susceptibility testing methods evaluated (created with BioRender.com)Figure 2.Biofilm phage susceptibility testing using biofilms grown on beads assessed in TSB medium using the Omnilog® (BBTO) method with phage SaMD22ø1. Results A comparison of result of testing of biofilms in wells and on beads and against planktonic bacteria is shown in Figure 3. Phage SaMD07ø1 showed no growth at 4 h; whereas phage SaRB105030ø5 showed ∼1-log decrease in CFUs at 4 h and ∼3-log decrease in CFUs at 8 h (Figure 3). BBTO hold-times of 37, 28 and 15 h were observed for phages SaMD07ø1, SaRB105030ø5 and phage K respectively. Phage SaMD22ø1 had an average hold time of 9 h and showed hold times >6 hours for all isolates tested (Figure 4). Microscopic inspection showed eradication of GFP-labelled MRSA biofilm by phage K (Figure 5).Figure 3.Results of quantitative culture of biofilms treated with phages SaMD07ø1 and SaRB105030ø5 in TSB medium.Panel 1 shows results of phage SaMD07ø1 with biofilms grown in wells (1a), on beads (1b) and planktonically (1c). Panel 2 shows results of phage SaRB105030ø5 with biofilms grown in wells (2a), on beads (2b) and planktonically (2c).Figure 4.Activity of phage SaMD22ø1 against biofilms formed by six MRSA strains determined using the Omnilog® (BBTO) method. The solid blue line indicates a hold time of 8 hours.Figure 5.Efficacy of Phage K to efficiently eradicate GFP-labelled MRSA strain AH1263 observed under the fluorescence microscope at 40X magnification. The authors are thankful to Dr. Alexander Horswill at University of Colorado for providing the GFP-labelled MRSA strain. Conclusion In conclusion, BBTO is a promising method for testing biofilm phage susceptibility although clinical correlation and testing of larger numbers of phage and bacterial isolates are needed. Disclosures Joseph Fackler, n/a, Adaptive Phage Therapeutics, Inc: Employee|Adaptive Phage Therapeutics, Inc: Stocks/Bonds John M. Sowers, n/a, Adaptive Phage Therapeutics: Employee|Adaptive Phage Therapeutics: Stocks/Bonds Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant